Dietary antioxidants and 10-year lung function decline in adults from the ECRHS survey

Abstract

The relationship between lung function decline and dietary antioxidants over 10 years in adults from three European countries was investigated.
In 2002, adults from three participating countries of the European Community Respiratory Health Survey (ECRHS) answered a questionnaire and underwent spirometry (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)), which were repeated 10 years later. Dietary intake was estimated at baseline with food frequency questionnaires (FFQ). Associations between annual lung function decline (mL) and diet (tertiles) were examined with multivariable analyses. Simes’ procedure was applied to control for multiple testing.
A total of 680 individuals (baseline mean age 43.8±6.6 years) were included. A per-tertile increase in apple and banana intake was associated with a 3.59 mL·year⁻¹ (95% CI 0.40, 7.68) and 3.69 mL·year⁻¹ (95% CI 0.25, 7.14) slower decline in FEV1 and FVC, respectively. Tomato intake was also associated with a slower decline in FVC (4.5 mL·year⁻¹; 95% CI 1.28, 8.02). Only the association with tomato intake remained statistically significant after the Simes’ procedure was performed. Subgroup analyses showed that apple, banana and tomato intake were all associated with a slower decline in FVC in ex-smokers.
Intake of fruits and tomatoes might delay lung function decline in adults, particularly in ex-smokers.

Full text

Dietary antioxidants and 10-year lung
function decline in adults from the
ECRHS survey
Vanessa Garcia-Larsen
1
, James F. Potts
2
, Ernst Omenaas
3
, Joachim Heinrich
4
,
Cecilie Svanes
5
, Judith Garcia-Aymerich
6
, Peter G. Burney
2,7
and
Deborah L. Jarvis
2,7
Affiliations:
1
Dept of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD,
USA.
2
Population Health and Occupational Disease Group, National Heart and Lung Institute, Imperial College
London, London, UK.
3
Centre for Clinical Research Haukeland University Hospital, Regional Health Authority
West, Bergen, Norway.
4
Ludwig-Maximilians-University (LMU), University Hospital, Institute of Occupational,
Social and Environmental Medicine, Member of Comprehensive Pulmonology Center (CPC-M), Munich,
Germany.
5
Centre for International Health, University of Bergen, Bergen, Norway.
6
Respiratory and
Environmental Health Research Unit, Municipal Institute of Medical Research (IMIM), Barcelona, Spain.
7
MRC-
PHE Centre for Environment and Health, Imperial College London, London, UK.
Correspondence: Vanessa Garcia-Larsen, Dept of International Health, Johns Hopkins Bloomberg School of
Public Health, 615 N Wolfe St, Suite E2546, Baltimore, MD 21205, USA. E-mail: vgla@jhu.edu
@ERSpublications
A higher intake of fruits and tomato is associated with a slower lung function decline, particularly in
ex-smokers http://ow.ly/5LLv30gK9Bn
Cite this article as: Garcia-Larsen V, Potts JF, Omenaas E, et al. Dietary antioxidants and 10-year lung
function decline in adults from the ECRHS survey. Eur Respir J 2017; 50: 1602286 [https://doi.org/10.1183/
13993003.02286-2016].
ABSTRACT The relationship between lung function decline and dietary antioxidants over 10 years in
adults from three European countries was investigated.
In 2002, adults from three participating countries of the European Community Respiratory Health
Survey (ECRHS) answered a questionnaire and underwent spirometry (forced expiratory volume in 1 s
(FEV1) and forced vital capacity (FVC)), which were repeated 10 years later. Dietary intake was estimated
at baseline with food frequency questionnaires (FFQ). Associations between annual lung function decline
(mL) and diet (tertiles) were examined with multivariable analyses. Simes’procedure was applied to
control for multiple testing.
A total of 680 individuals (baseline mean age 43.8±6.6 years) were included. A per-tertile increase in
apple and banana intake was associated with a 3.59 mL·year
−1
(95% CI 0.40, 7.68) and 3.69 mL·year
−1
(95% CI 0.25, 7.14) slower decline in FEV1and FVC, respectively. Tomato intake was also associated with
a slower decline in FVC (4.5 mL·year
−1
; 95% CI 1.28, 8.02). Only the association with tomato intake
remained statistically significant after the Simes’procedure was performed. Subgroup analyses showed that
apple, banana and tomato intake were all associated with a slower decline in FVC in ex-smokers.
Intake of fruits and tomatoes might delay lung function decline in adults, particularly in ex-smokers.
This article has supplementary material available from erj.ersjournals.com
Received: Nov 21 2016 | Accepted after revision: Sept 22 2017
Copyright ©ERS 2017. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
https://doi.org/10.1183/13993003.02286-2016 Eur Respir J 2017; 50: 1602286
|
ORIGINAL ARTICLE
LUNG FUNCTION

Introduction
Lung function is a predictor of mortality in the general population, as well as in patients with lung disease,
even in those who have never smoked [1]. Maintaining lung function is an important goal in the
prevention of chronic respiratory diseases and a major public health objective; yet, smoking cessation
remains the main target to reduce the burden of these diseases [2].
The possible modulatory effect of diet on lung health has been investigated in several epidemiological
studies, suggesting that dietary intake of various sources of antioxidants are associated with improved
ventilatory function outcomes in adults [3]. Cross-sectional and longitudinal evidence has shown a
positive association between forced vital capacity (FVC) and higher fruit and flavonoid intake in young
[4], middle-aged [5] and elderly adults [6]. Similarly, in older adults, a ‘prudent’dietary pattern,
characterised by a higher intake of fruits and vegetables, has been associated with better lung function and
a lower prevalence of chronic obstructive pulmonary disease (COPD) [7]. Longitudinal evidence is less
consistent for other antioxidants. A 4-year follow-up study showed that having a higher intake of
antioxidant nutrients was associated with an attenuated decline of forced expiratory volume in 1 s (FEV1)
in ex- and current-smokers, compared to those who had a lower intake [8], whilst other studies have
shown a positive association between serum vitamin E [9] and lung function decline, or no effect of
vitamin E supplementation on lung function [10].
The European Community Respiratory Health Survey (ECRHS) is a three-phased, longitudinal,
multi-centre, European cohort study that examines the role of environmental risk factors on respiratory
health. In the present study, we sought to investigate whether a higher intake of dietary sources of
antioxidants in middle-aged European adults could attenuate ageing-related lung function decline over
10 years.
Methods
Sample
The ECRHS survey started in 1990, with outcomes and exposures studied at three time points: 1990–1995
(ECRHS I), 2002 (ECRHS II) and 2012 (ECRHS III). Details of the study design have been reported
elsewhere [11, 12]. Briefly, in 29 participant centres in 1990, a random sample of at least 3000 adults, aged
20–44 years was selected, using a local sampling frame. From those who responded, a random sample of at
least 600 adults was selected to undergo a detailed clinical examination (1991–1993). In ECRHS II (1998–
2002), participants who had completed the extended questionnaire in ECRHS I, were reinvestigated to
include spirometry. In ECRHS III, those who took part in the clinical stages of ECRHS I and II were again
contacted, and responders were invited to a local testing centre, where measures of lung function were
carried out once more. Figure 1 illustrates the flowchart of participants from ECRHS I to those included in
the present analysis (ECRHS II and III).
Assessment of diet
Dietary assessments were included in ECRHS II at five centres (three countries), although the method and
protocol differed among countries. For the current analyses, we present the results from these centres. The
same centres also participated in ECRHS III (Hamburg and Erfurt in Germany; Ipswich and Norwich in
the UK; and Bergen in Norway).
Food frequency questionnaires (FFQ)
The German FFQ was developed for use in the German part of the European Prospective Investigation
into Cancer and Nutrition (EPIC-Heidelberg) [13]. It recorded the consumption of 158 different foods
over the previous 12 months as frequencies (zero to five or more portions per day). Portion size was
selected from multiple-choice questions, sometimes with reference photos. Supplementary questions
covered aspects of diet, such as the preparation and fat content of foods. The FFQ was distributed after the
Support statement: The current study is part of the Ageing for Lungs in European Cohorts (ALEC) study. The ALEC
Study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement
no. 633212. The coordination of the ECRHS II was supported by the European Commission, as part of their Quality of
Life programme. The following bodies funded the local studies in ECRHS II included in this paper. Bergen: Norwegian
Research Council, Norwegian Asthma and Allergy Association (NAAF), Glaxo Wellcome AS, Norway Research Fund.
Erfurt: GSF-National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (DFG) (grant
code FR 1526/1-1). Hamburg: GSF-National Research Centre for Environment and Health, Deutsche
Forschungsgemeinschaft (DFG) (grant code MA 711/4-1). Ipswich and Norwich: Asthma UK ( formerly known as
National Asthma Campaign (UK)). ECRHS III was funded by the Medical Research Council (Grant Number 92091).
Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: None declared.
https://doi.org/10.1183/13993003.02286-2016 2
LUNG FUNCTION | V. GARCIA-LARSEN ET AL.

clinical and questionnaire assessments, and the participants were asked to return the completed FFQ by
mail. Further details on the characteristics of the FFQs, exclusion of dietary data and the validity and
repeatability of the FFQs are provided in the supplementary material.
Exclusion of dietary data
On the FFQs, respondents sometimes left individual items blank. This was assumed to denote zero intake
of these foods; however, if 20% of the items were blank, the FFQ was considered incomplete, and the
subject was excluded from further analyses. Participants were also excluded if they had extreme values of
total energy intake, which might suggest an unrealistic response. We calculated the expected basal
metabolic rate (BMR) with the given age, weight and sex [4], and excluded subjects with a ratio of energy
intake to expected BMR that was either below the 0.5th sample centile or above the 99.5th sample centile
for their country [5]. This is what we referred to as having “unrealistic total energy intake (TEI)”.
Nutrient intakes
Nutrient intakes were calculated for each country from the FFQ data and supplementary questions, using
local food tables [14–16]. The intake of nutrients with antioxidant properties was measured by whole food
intake (total fruit and total vegetable intakes) and micronutrient intake, calculated from all dietary sources
of antioxidant vitamin intake (vitamins C and E, and β-carotene). In addition to total fruit and vegetable
intake, we selected 17 individual fruits (n=5), vegetables (n=5), or other foods or beverages (n=7) for their
high content of β-carotene and vitamin C [15], and because they generally have the highest estimates of
total flavonoids, or for their reported potential antioxidant effects on lung health [5].
Lung function measurements
During ECRHS II and ECRHS III, lung function measurements of the participants were taken. During
ECRHS II, participants had at least five, and up to nine attempts to provide two technically satisfactory
forced expiratory manoeuvres. In 2002 (ECRHS II), different spirometers were used at each centre
(Biomedin in the UK, Sensor Medics in Norway and Jaeger Pneumolab in Germany); however, during
Participants with complete FFQ data
Germany
1983
Norway
835
UK
921
Germany
590
Norway
596
Subjects who participated in ECRHS I
and who were invited to take part in
ECRHS II
Subjects who answered the main
ECRHS II questionnaire
UK
554
Germany
390
Norway
551
UK
241
Participants with realistic TEI
estimates and valid lung function
Germany
388
Norway
547
UK
239
Germany
372
Norway
539
UK
221
Germany
244
ECRHS III
ECRHS II
ECRHS I
Norway
312
UK
124
Participants with realistic
TEI estimates
Participants with realistic TEI estimates and valid lung function at follow-up
FIGURE 1 Flowchart of participants in European Community Respiratory Health Survey (ECRHS) II and ECRHS III surveys included in the present
study. FFQ: food frequency questionnaires; TEI: total energy intake
https://doi.org/10.1183/13993003.02286-2016 3
LUNG FUNCTION | V. GARCIA-LARSEN ET AL.

ECRHS III, lung function was tested at all centres using the NDD spirometer (ndd Medical Technologies,
Zurich, Switzerland). During ECRHS II, participants had at least five, and up to eight attempts to provide
reproducible (150 mLs) FEV1and FVC. The maximum FEV1and FVC reproducible to 150 mL, possibly
coming from different expiratory manoeuvres [17], were used as the outcome. Decline in FEV1and FVC
was expressed per year of follow-up (ECRHS III value minus ECRHS II value, a negative value represented
a decline). All measures were assessed pre-bronchodilator.
Potential confounders
Body mass index (BMI) was based on the measured weight and height. Subjects were categorised as
never-, ex- or current smokers based on questionnaire responses. Pack-years of smoking were calculated,
based on questions about ever-smoking; and among smokers, additional questions about age at which
smoking commenced, current smoking, reducing or quitting smoking were posed. Educational level was
estimated as the age at which full-time education was completed, and three categories were created
(completed education before 18 years of age, between 18–21 years, or >21 years). Socio-economic status
was based on the reported occupation group of the International Standard Classification of
Occupations-88 codes [18]. Physical activity was based on the reported frequency of physical exercise (the
question “How often do you usually exercise so much that you get out of breath or sweat?”was posed),
and categorised as follows: never; less than once a week; one to three times a week; or more than three
times a week.
Statistical analyses
The total intake in grams of fruits and vegetables, as well as the fifteen individual food items analysed, was
considered as tertiles. The decline in FEV1and FVC in mL per year between ECRHS II and ECRHS III
per tertile of each food consumed was assessed using multivariate linear regression, controlling for two
sets of confounders; a baseline model (Model 1) included the covariates age, height and country (results
presented in the supplementary material). Model 2 added the covariates sex, BMI, socio-economic status,
physical activity, years of education and TEI. Data from centres within the same country were merged
and treated as a single sample in the analyses. The Simes’procedure was used to adjust for multiple
testing [19].
All analyses were repeated and stratified by country, and the effect estimates were combined using random
effects meta-analysis [20]. Heterogeneity was summarised using the I
2
statistic [21]. Further analyses were
carried out after stratifying by smoking status, using the same models of adjustment as those used with the
dietary exposures that showed a statistically significant association in the analyses of the whole sample. All
analyses were conducted using Stata 14 (Stata Corporation, College Station, TX, USA).
Results
Figure 1 shows the number of participants per country. Clinical and questionnaire assessments were
available for 1740 subjects from ECRHS II. Of the 1182 subjects with complete FFQ data, i.e. subjects with
more than 80% of the FFQ completed, eight subjects were further excluded for having an “unrealistic TEI”
(n=1174). Then, 42 subjects were also excluded for not having valid lung function measures, leaving 1132
subjects with realistic TEI and valid lung function data in the ECRHS II. Of this sample, at the time of
follow-up (ECRHS III), 680 individuals had valid lung function measured at this second time point, and
comprised the final sample for analysis. The general characteristics of responders (ECRHS III) and
non-responders were similar between both groups, in relation to age, sex, socio-economic status, BMI and
physical activity (Supplementary table S1).
Table 1 summarises the main general characteristics and dietary intake of participants with FFQ at
baseline and lung function at baseline and during ECRHS III (n=680). The average age at baseline was
43.8±6.6 years. Over 40% of the participants had smoked at some point before ECRHS III, and 16% were
current smokers. The mean decline in FEV1and FVC in the present study sample over the 10-year period
was 445 mL and 389 mL, respectively. The median total intake of fruits and vegetables was 278 g·day
−1
and 114 g·day
−1
, respectively, with the highest consumption in Norway.
Table 2 shows the adjusted associations between annual FEV1and FVC decline, and dietary intake of the
relevant foods and antioxidant vitamins over the 10-year follow-up. In the fully adjusted model, total
intake of fruits was positively associated with a 3.5 mL·year
−1
slower decline in FEV1(95% CI 0.04, 6.92);
however, the association was of borderline statistical significance. Similarly, per-tertile increases in the
intake of apples, bananas, tomatoes, herbal tea and vitamin C were all significantly associated with a
slower decline in FVC. Among these, only the association between FVC and tomato intake survived the
Simes’procedure (4.74 mL·year
−1
slower decline in FVC; 95% CI 1.35, 8.13).
https://doi.org/10.1183/13993003.02286-2016 4
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As IgE-sensitisation to airborne allergens, such as birch pollen could affect the intake of some fruits
through cross-reactivity, we further investigated whether IgE sensitisation could be a confounder in the
associations investigated. The effect sizes for the associations between total fruit intake (per-tertile
increase) and FEV1was 2.74 mL (95% CI 0.08, 5.4), p=0.04; and FVC, 3.21 mL (95% CI −0.02, 6.72),
p=0.055 (data not shown).
The hypothesis that smoking modifies the effects of dietary antioxidants was investigated within
categories of cigarette smokers (current, ex- (prior to ECRHS III) and never-smokers). Tables 3 and 4
show the adjusted stratified analyses according to smoking habit for the dietary exposures that showed a
statistically significant association in the analyses presented in table 2. Total dietary intake of fruits,
apples, tomatoes and herbal tea were all associated with a slower decline in FEV1and FVC in
ex-smokers (p<0.05); however, no effect was observed in never- or current smokers (table 3). There was
evidence that smoking modified the effect of fruit intake on FEV1and FVC decline ( p for
interaction=0.03, and p for interaction=0.04, respectively); however, smoking did not modify the effect
of tomatoes, herbal tea, or vitamin C (all p for interaction >0.05). Direction and magnitude of effects
seen in ex- and current smokers were only slightly altered by further adjustment for pack-years of
smoking (table 4).
In a post-hoc analysis, we examined the effect of total intake of fruits, apples, and tomatoes on FEV1and
FVC per country, and pooled the effect estimates. A trend towards an association between higher intake of
these foods and a slower decline of both spirometric measures, with little or no heterogeneity among
countries was observed, although the overall estimate did not reach significance (Supplementary
figures S1–S4).
TABLE 1 General characteristics of participants in ECRHS II and ECRHS III with FFQ and lung function measures
Variables (measured in 2002) Countries
Germany UK Norway Overall
Subjects n 244 124 312 680
Mean±SD years of follow-up ECRHS II and III 10.3±0.4 12.6±0.5 9.3±0.2 10.3±1.2
Mean±SD age years 44.2±7.0 43.3±6.2 43.6±6.5 43.8±6.6
Males n (%) 115 (47.1) 54 (43.6) 167 (53.5) 336 (49.4)
Mean±SD height m 1.71±0.1 1.68±0.1 1.73±0.1 1.71±0.1
Mean±SD BMI kg·m
−2
25.7±4.5 26.10±4.4 25.6±4.0 25.7±4.2
Smoking
#
n (%)
Never-smokers 82 (33.8) 74 (59.7) 126 (41.6) 282 (42.2)
Ex-smokers gave up before ECRHS II 94 (38.9) 36 (29.0) 74 (24.4) 204 (30.5)
Ex-smokers gave up after ECRHS II 21 (8.7) 7 (5.7) 42 (13.9) 70 (10.5)
Current smokers 45 (18.6) 7 (5.7) 61 (20.1) 113 (16.9)
Mean number of pack-years smoked up to ECRHS III
¶
21.7 14.7 20.1 20.1
Age when completed education years
+
n (%)
Before 18 112 (17.1)
18–20 213 (32.7)
⩾21 327 (50.2)
FEV1at baseline (mean z-score GLI) 0.25 0.15 −0.39 −0.06
FVC at baseline (mean z-score GLI) 0.14 0.31 −0.12 0.05
Whole sample 10-year mean±SD change in FEV1mL
§
−445.6±290.0
Whole sample 10-year mean±SD change in FVC mL
§
−381.1±347.9
Median (IQR) total fruit intake g·day
−1
205.9 (116.4–347.0) 289.8 (175.4–442.7) 321.5 (191.7–502.6) 278.5 (156.5–443.9)
Median (IQR) total vegetable intake g·day
−1
69.6 (51.8–95.9) 155.8 (107.9–225.4) 180.4 (97.5–319.8) 114.3 (69.7–213.3)
Median (IQR) vitamin A IU 872.6 (570–1381) 545.9 (375–844) 482.4 (291–872) 633.6 (376–113)
Median (IQR) vitamin C mg 104.1 (76.5–145.5) 225.2 (151.2–348.9) 230.0 (148.6–340.8) 170.8 (105.8–273.1)
Median (IQR) vitamin D µg 3.4 ((2.3–4.8) 2.7 (1.9–3.5) 4.5 (3.3–6.4) 3.7 (2.5–5.4)
Median (IQR) vitamin E µg 8.7 (6.7–10.4) 8.7 (6.3–11.0) 13.6 (10.1–18.1) 10.1 (7.4–14.4)
Median (IQR) total energy intake kcal 2251 (1470–3069) 2587 (1788–3386) 2819 (1710–3918) 2573 (1748–3421)
ECRHS: European Community Respiratory Health Survey; FFQ: food frequency questionnaires; BMI: body mass index; FEV1: forced expiratory
volume in 1 s; GLI: Global Lung Function Initiative; FVC: forced vital capacity; IQR: interquartile range.
#
: Smoking status was based on
self-report in 2000 and 2013. Current smokers were defined as those who smoked in 2000 and 2013. Ex-smokers were split into two groups:
those who had quit before baseline and those who quit between baseline and follow-up. Never-smokers reported no smoking at both
instances.
¶
: Estimated for ever-smokers.
+
: From 652 subjects with information on number of years of education who had lung function data in
ECRHS II and III.
§
: Standardised to a 10-year interval period.
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LUNG FUNCTION | V. GARCIA-LARSEN ET AL.

Discussion
Our findings suggest that a higher total intake of fruits, and of apples in middle-aged adults in Europe,
was associated with a slower FEV1decline; whilst the intake of apples, bananas, tomatoes, herbal tea and
vitamin C was associated with a slower FVC decline. These associations remained robust even after
adjustment for relevant potential confounders, and our results suggest that these protective effects are
likely of greater impact in those who have quit smoking. The intake of fruits and vegetables in the adult
participants of the present study averaged just over 400 g (four fruits), with Germany reporting the lowest
intake (265 g) and Norway reporting the highest (445 g).
Ageing and smoking are established risk factors for a steeper lung function decline in adults [22]; the role
of diet, however, is less clear [23]. Evidence from randomised controlled trials (RCTs) is limited to very
few studies, which have shown no effect of β-carotene or α-tocopherol [24, 25] on lung function. These
studies have used very specific adult populations affected by serious comorbidities, and are not
representative of the general population. More recently, an intervention using vitamin E and selenium
showed no effect on lung function in healthy adults and smokers [10]. Observational evidence suggests
that the intake of foods that are rich in antioxidants (e.g. fruits and vegetables), as well as specific
antioxidants, is associated with a slower decline in lung function in adults [26].
We found associations between tomato intake and a slower decline in both FEV1and FVC in the whole
sample, and particularly in ex-smokers. Tomatoes are the richest dietary sources of lycopene [27], a
carotenoid with no vitamin A activity. This might explain why we observed beneficial associations with
this food, but not with vitamin A or other sources of this antioxidant. A RCT in asthmatic adults showed
that a diet low in antioxidants reduced FEV1and FVC % predicted values [28], and that intake of a
tomato extract and tomato juice for 10 days led to reduced airway inflammation in the intervention group
[29]. The potential benefits of lycopene in lung health might extend to reduction of the risk of mortality
TABLE 2 Adjusted associations of FEV1and FVC decline with dietary intake measured at baseline (2001)
Dietary intake (per-tertile increase) FEV1decline mL·year
−1
(continuous)
regression coefficient (95% CI)
FVC decline mL·year
−1
(continuous)
regression coefficient (95% CI)
Fully adjusted model
#
p-value Fully adjusted model
¶
p-value
Foods g
Total fruit 2.99 (0.37, 5.61) 0.025 3.48 (0.04, 6.92) 0.048
Apple 2.53 (0.10, 4.94) 0.04 3.96 (0.76, 7.15) 0.01
Banana 2.57 (−0.02, 5.17) 0.05 3.97 (0.51, 7.43) 0.03
Orange 2.40 (−0.07, 4.87) 0.06 2.94 (−0.33, 6.21) 0.08
Pear 2.19 (−0.80, 5.17) 0.15 1.28 (−2.66, 5.22) 0.52
Berries 0.52 (−2.31, 3.35) 0.72 1.59 (−2.11, 5.29) 0.40
Total vegetables −0.29 (−3.47, 2.89) 0.86 −0.01 (−4.26, 4.25) 0.96
Potato (boiled/mashed/baked) −1.83 (−4.47, 0.82) 0.18 −3.27 (−6.78, 0.24) 0.07
Broccoli, cabbage and cauliflower −1.26 (−4.44, 1.93) 0.44 −2.94 (−7.21, 1.32) 0.18
Carrots 0.72 (−2.09, 3.53) 0.61 −0.86 (−4.59, 2.87) 0.65
Garlic −0.45 (−3.26, 2.35) 0.75 −0.02 (−3.66, 3.70) 0.99
Tomato 2.80 (0.23, 5.38) 0.03 4.74 (1.35, 8.13) 0.006
+
Flavonoid-rich foods/beverages mL or g
Chocolate −0.35 (−3.10, 2.39) 0.80 −2.26 (−5.89, 1.36) 0.22
Nut −0.82 (−4.14, 6.77) 0.63 −1.72 (−3.67, 10.70) 0.34
Lentils, dahl, mixed beans 1.31 (−4.28, 6.60) 0.68 −3.51 (−6.6, 0.23) 0.07
Tea (black and green) −1.43 (−4.01, 1.15) 0.28 −2.59 (−6.01, 0.83) 0.14
Herbal tea 4.64 (−0.23, 9.53) 0.06 7.75 (1.28, 14.2) 0.02
Coffee 1.05 (−1.51, 3.60) 0.42 1.35 (−2.01, 4.70) 0.43
Wine 0.59 (−1.96, 3.14) 0.65 3.62 (−3.56, 10.8) 0.32
Antioxidant vitamins
Vitamin A (retinol) UI 0.72 (−3.10, 2.73) 0.90 0.17 (−3.66, 4.00) 0.77
Vitamin A (β-carotenoid) UI −0.19 (−0.59, 2.11) 0.61 0.02 (−3.82, 3.87) 0.99
Vitamin C (ascorbic acid) mg 2.64 (−0.91, 5.86) 0.11 4.54 (0.28, 8.82) 0.037
Vitamin D µg −2.66 (−5.60, 0.29) 0.08 −1.17 (−5.07, 2.73) 0.56
Vitamin E µg 0.17 (−3.40, 3.75) 0.93 0.58 (−4.17, 5.34) 0.81
Fully adjusted model (adjusted for height, age, country, sex, smoking status, socio-economic class, body mass index, total energy intake,
physical activity and years of education). Bold font indicates a statistically significant p-value (<0.05). FEV1: forced expiratory volume in 1 s; FVC:
forced vital capacity.
#
: n=680;
¶
: n=654;
+
: Only dietary exposure to survive Simes’procedure (p=0.03).
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LUNG FUNCTION | V. GARCIA-LARSEN ET AL.

TABLE 3 Adjusted associations
#
between FEV1or FVC decline and dietary intake in adults stratified by smoking status with
dietary data collected in 2001
Dietary intake
(per-tertile
increase)
Average decline in lung function mL·year
−1
(continuous)
regression coefficient (95% CI)
Never-smoker p-value Quit before ECRHS III p-value Smoker p-value p-value for interaction
Subjects n 270 255 109
FEV1
Total fruit g 0.51 (−3.62, 4.65) 0.81 6.41 (2.29, 10.5) 0.002 3.83 (−2.93, 10.60) 0.26 0.03
Apple g 0.16 (−3.51, 3.82) 0.93 4.79 (0.87, 8.72) 0.017 0.62 (−6.22, 7.46) 0.86 0.09
Banana g 2.63 (−1.11, 6.37) 0.17 2.92 (−1.52, 7.35) 0.20 −0.82 (−7.70, 6.06) 0.81 0.25
Tomato g 0.52 (−3.36, 4.40) 0.79 5.15 (0.87, 9.44) 0.019 5.71 (−1.21, 12.63) 0.11 0.06
Herbal tea mL −3.89 (−11.5, 3.71) 0.32 12.8 (5.13, 20.54) 0.001 1.97 (−13.36, 17.3) 0.80 0.21
Vitamin C mg 1.66 (−3.36, 6.69) 0.52 3.99 (−1.45, 9.44) 0.15 3.19 (−5.59, 11.97) 0.47 0.05
FVC
Total fruit g 0.13 (−4.79, 5.06) 0.96 8.13 (2.22, 14.01) 0.007 4.15 (−5.41, 13.7) 0.39 0.04
Apple g 1.45 (−2.91, 5.80) 0.51 6.75 (1.14, 12.34) 0.018 0.78 (−9.13, 10.69) 0.88 0.29
Banana g 4.07 (−0.54, 8.67) 0.08 6.23 (0.01, 12.5) 0.05 −3.79 (−13.6, 5.99) 0.44 0.04
Tomato g 1.02 (−3.66, 5.70) 0.67 9.09 (3.04, 15.14) 0.003 7.16 (−3.05, 17.37) 0.17 0.11
Herbal tea mL −2.52 (−11.7, 6.67) 0.59 14.4 (3.16, 25.69) 0.01 12.34 (−9.47, 34.15) 0.26 0.11
Vitamin C mg 3.17 (−2.83, 9.16) 0.30 4.65 (−3.08, 12.37) 0.24 10.58 (−1.96, 23.11) 0.10 0.30
Bold font indicates a statistically significant p-value (<0.05). FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ECRHS: European
Community Respiratory Health Survey.
#
: Adjusted for height, age, country, sex, socio-economic status, body mass index, total energy intake,
years of education and physical activity.
TABLE 4 Adjusted associations of FEV1or FVC decline with dietary intake as reported in 2001
(controlling for lifetime pack-years of smoking at follow-up)
#
Dietary exposures (tertiles) Decline in lung function mL·year
−1
(continuous)
regression coefficient (95% CI)
Quit before ECRHS III p-value Smoker p-value
Subjects n 227 95
FEV1
Total fruit g 5.45 (1.12, 9.78) 0.01 1.21 (−5.92, 8.33) 0.74
Apple g 4.97 (0.94, 9.01) 0.016 6.95 (−0.84, 14.73) 0.08
Banana g 1.41 (−3.21, 6.04) 0.55 −3.22 (−10.28, 3.83) 0.37
Tomato g 5.44 (0.98, 9.90) 0.017 3.63 (−3.60, 10.86) 0.32
Herbal tea mL 12.03 (4.09, 19.98) 0.003 2.64 (−14.66, 19.94) 0.76
Vitamin C mg 2.83 (−2.90, 8.57) 0.33 0.93 (−8.07, 9.92) 0.84
FVC
Total fruit g 7.38 (1.17, 13.6) 0.02 1.47 (−8.91, 11.9) 0.78
Apple g 7.28 (1.59, 13.0) 0.01 6.41 (−5.38, 18.2) 0.28
Banana g 4.67 (−1.88, 11.2) 0.16 −7.44 (−17.4, 2.48) 0.14
Tomato g 8.45 (2.16, 14.7) 0.009 5.12 (−4.93, 15.2) 0.31
Herbal tea mL 11.57 (−0.01, 23. 15) 0.05 14.93 (−8.90, 38.76) 0.22
Vitamin C mg 2.80 (−5.24, 10.8) 0.49 6.90 (−6.43, 20.23) 0.31
Adjusted for height, age, country, sex, social class, body mass index, total energy intake, years of education
and physical activity. Bold font indicates a statistically significant p-value (<0.05). FEV1: forced expiratory
volume in 1 s; FVC: forced vital capacity.
#
: Only ex- or current smokers included in this analysis).
https://doi.org/10.1183/13993003.02286-2016 7
LUNG FUNCTION | V. GARCIA-LARSEN ET AL.

in individuals with COPD. A longitudinal analysis based on the National Health and Nutrition
Examination Survey (NHANES) III study showed that serum levels of lycopene and vitamin C were the
only antioxidants to be negatively associated with the risk of all-cause mortality in fully adjusted regression
models [30]. Serum lycopene and pro-vitamin carotenoids were also negatively associated with FEV1and
FVC decline over 14 years in young adults [31].
Given our a priori hypothesis that antioxidant intake might contribute to the preservation of lung function
and attenuation of decline, we also investigated the association between specific food items and a high
content of flavonoids. Flavonoids are widely distributed in plant foods and are found in particularly high
amounts in fruits, vegetables and herbal teas [32]. Intervention studies in adults have demonstrated their
antioxidant properties [33], and extensive experimental evidence demonstrates their anti-inflammatory
effects [34], a mechanism through which they might exert beneficial effects on lung health. The scant
evidence from population-based studies so far, suggests that catechins are positively associated with higher
ventilatory function in adults [4, 5], and pro-anthocyanidins are prospectively associated with a
slower lung function decline in older adults [6]. Albeit we found no evidence of an association between
these foods and lung function decline, our observation that total fruit intake is associated with a slower
decline in FEV1and FVC might be partly explained by the flavonoid contents in this food group. Our
observation that herbal tea intake is associated with a slower lung function decline further supports
the notion that regular consumption of foods rich in polyphenolic compounds is beneficial for lung
health [35, 36].
Our results show that the effects observed for apples, tomato and herbal tea were particularly strong in
ex-smokers, regardless of the number of pack-years smoked between the two surveys. The Health Aging
and Body Composition (Health ABC) study, a population-based survey in older adults, also showed that a
higher intake of antioxidant nutrients was associated with a slower lung function decline (only FEV1
measured) [8]. Similarly, earlier studies on dietary antioxidant intake and lung function decline have
reported similar effects to those found in our study. A study in middle-aged Welshmen (45–59 years old)
followed for 5 years, reported a 10–15 mL·year
−1
slower decline in FEV1in those with the highest versus
those with the lowest intakes of apples; however, no effect was observed for the antioxidant vitamins C or
E [37]. In the Health ABC study, a higher intake of fruits or vegetables was associated with an 18 mL and
24 mL·year
−1
slower decline in FEV1, respectively, in older adults [8]. In our study, the effect size was
smaller, but there was a longer follow-up time.
One strength of this study is the use of a random community-based sample of adults from three European
countries, which affords some confidence in generalising the results to wider populations. Lung function
was measured with standardised protocols at baseline and at follow-up, with a quality control programme
in place. At follow-up, visual quality control of forced expiratory curves was conducted. Given the various
dietary exposures being tested and the fact that we individually investigated the possible association
between single nutrients and outcomes, we used the Simes’procedure as a more rigorous way to control
for multiple comparisons, to reduce the possibility of false discovery. The FFQ used in this study was
previously validated in a similar population of adults from the participating countries, showing a good
level of reproducibility and validity [38]. One limitation of the study is that we only had dietary
assessments at baseline on one occasion for the three countries. We had to assume that diet remained
relatively constant in adult life, and evidence for this exists [39]. Investigations of the association between
single nutrients and disease might not accurately reflect a specific dietary habit or dietary behaviour, as
neither foods, nor nutrients are consumed in isolation. Information on nutrient supplementation was not
collected, and we cannot rule out whether adjustment for this might have altered estimates. However,
studies on nutrient supplementation and lung function have shown little evidence of an association [10].
In conclusion, our study suggests that dietary factors might play a role in preserving ventilatory function
in adults, by slowing down a decline in lung function. In particular, dietary antioxidants possibly
contribute to restoration, following damage caused by exposure to smoking, among adults who have quit.
Acknowledgements
We are indebted to the participants of ECRHS II and III for their willingness to help with the collection of data.
References
1Strachan DP. Ventilatory function, height, and mortality among lifelong non-smokers. J Epidemiol Community
Health 1992; 46: 66–70.
2Young RP, Hopkins, RJ. Primary and secondary prevention of chronic obstructive pulmonary disease: where to
next? Am J Respir Crit Care Med. 2014; 190: 839–840.
3Hanson C, Rutten EP, Wouters EF, et al. Diet and vitamin D as risk factors for lung impairment and COPD.
Transl Res 2013; 162: 219–236.
https://doi.org/10.1183/13993003.02286-2016 8
LUNG FUNCTION | V. GARCIA-LARSEN ET AL.

4Garcia-Larsen V, Amigo H, Bustos P, et al. Ventilatory function in young adults and dietary antioxidant intake.
Nutrients 2015; 7: 2879–2896.
5Tabak C, Smit HA, Heederik D, et al. Diet and chronic obstructive pulmonary disease: independent beneficial
effects of fruits, whole grains, and alcohol (the MORGEN study). Clin Exp Allergy 2001; 31: 747–755.
6Mehta AJ, Cassidy A, Litonjua AA, et al. Dietary anthocyanin intake and age-related decline in lung function:
longitudinal findings from the VA Normative Aging Study. Am J Clin Nutr 2016; 103: 542–550.
7Shaheen SO, Jameson KA, Syddall HE, et al. The relationship of dietary patterns with adult lung function and
COPD. Eur Respir J 2010; 36: 277–284.
8Bentley AR, Kritchevsky SB, Harris TB, et al. Dietary antioxidants and forced expiratory volume in 1 s decline: the
Health, Aging and Body Composition study. Eur Respir J 2012; 39: 979–984.
9Hanson C, Lyden E, Furtado J, et al. Serum tocopherol levels and vitamin E intake are associated with lung
function in the normative aging study. Clin Nutr 2016; 35: 169–174.
10 Cassano PA, Guertin KA, Kristal AR, et al. A randomized controlled trial of vitamin E and selenium on rate of
decline in lung function. Respir Res 2015; 16: 35.
11 Burney PG, Luczynska C, Chinn S, et al. The European Community Respiratory Health Survey. Eur Respir J 1994;
7: 954–960.
12 The European Community Respiratory Health Survey II. Eur Respir J 2002; 20: 1071–1079.
13 Bohlscheid-Thomas S, Hoting I, Boeing H, et al. Reproducibility and relative validity of energy and macronutrient
intake of a food frequency questionnaire developed for the German part of the EPIC project. European
Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 1997; 26: Suppl. 1, S71–S81.
14 (BgVV) FIfHPoC. Der Bundeslebensmittelschlussel (BLS II.3). [The German Food Code and Nutrient Database].
Berlin, BgVV, 1999.
15 McCance R. McCance and Widdowson’s the Composition of Foods. 6th Summary Edn. Cambridge, Royal Society
of Chemistry, 2002.
16 Norwegian Food Safety Authority DfHaSA, and University of Oslo http://matportalen.no/matvaretabellenn 2006
Date last accessed: October 17, 2016. Date last updated: 2017.
17 American Thoracic Society. Standardization of Spirometry, 1994 Update. Am J Respir Crit Care Med 1995; 152:
1107–1136.
18 International Labour Organisation. International Standard Classification of Occupations (ISCO-88). Geneva,
International Labour Organisation, 1991.
19 Simes RJ. An improved Bonferroni procedure for multiple tests of significance. Biometrika 1986; 73: 4.
20 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.
21 Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.
22 Lee PN, Fry JS. Systematic review of the evidence relating FEV1decline to giving up smoking. BMC Med 2010; 8:
84.
23 Eisner MD, Anthonisen N, Coultas D, et al. An official American Thoracic Society public policy statement: novel
risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 182:
693–718.
24 Rautalahti M, Virtamo J, Haukka J, et al. The effect of alpha-tocopherol and beta-carotene supplementation on
COPD symptoms. Am J Respir Crit Care Med 1997; 156: 1447–1452.
25 Agler AH, Kurth T, Gaziano JM, et al. Randomised vitamin E supplementation and risk of chronic lung disease in
the Women’s Health Study. Thorax 2011; 66: 320–325.
26 Carey IM, Strachan DP, Cook DG. Effects of changes in fresh fruit consumption on ventilatory function in healthy
British adults. Am J Respir Crit Care Med 1998; 158: 728–733.
27 Agarwal S, Rao AV. Tomato lycopene and its role in human health and chronic diseases. CMAJ 2000; 163:
739–744.
28 Wood LG, Garg ML, Smart JM, et al. Manipulating antioxidant intake in asthma: a randomized controlled trial.
Am J Clin Nutr 2012; 96: 534–543.
29 Wood LG, Garg ML, Powell H, et al. Lycopene-rich treatments modify noneosinophilic airway inflammation in
asthma: proof of concept. Free Radic Res 2008; 42: 94–102.
30 Ford ES, Li C, Cunningham TJ, et al. Associations between antioxidants and all-cause mortality among US adults
with obstructive lung function. Br J Nutr 2014; 112: 1662–1673.
31 Thyagarajan B, A Meyer K, Smith LJ, et al. Serum carotenoid concentrations predict lung function evolution in
young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Clin Nutr 2011; 94:
1211–1218.
32 Manach C, Scalbert A, Morand C, et al. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79:
727–747.
33 Riso P, Klimis-Zacas D, Del Bo C, et al. Effect of a wild blueberry (Vaccinium angustifolium) drink intervention
on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors.
Eur J Nutr 2013; 52: 949–961.
34 Leyva-Lopez N, Gutierrez-Grijalva EP, Ambriz-Perez DL, et al. Flavonoids as cytokine modulators: a possible
therapy for inflammation-related diseases. Int J Mol Sci 2016; 17: 921.
35 Ghasemi Pirbalouti A, Siahpoosh A, Setayesh M, et al. Antioxidant activity, total phenolic and flavonoid contents
of some medicinal and aromatic plants used as herbal teas and condiments in Iran. J Med Food 2014; 17:
1151–1157.
36 Yin DD, Yuan RY, Wu Q, et al. Assessment of flavonoids and volatile compounds in tea infusions of water lily
flowers and their antioxidant activities. Food Chem 2015; 187: 20–28.
37 Butland BK, Fehily AM, Elwood PC. Diet, lung function, and lung function decline in a cohort of 2512 middle
aged men. Thorax 2000; 55: 102–108.
38 Hooper R, Heinrich J, Omenaas E, et al. Dietary patterns and risk of asthma: results from three countries in
European Community Respiratory Health Survey-II. Br J Nutr 2010; 103: 1354–1365.
39 Westerterp KR. Metabolic adaptations to over--and underfeeding--still a matter of debate? Eur J Clin Nutr 2013;
67: 443–445.
https://doi.org/10.1183/13993003.02286-2016 9
LUNG FUNCTION | V. GARCIA-LARSEN ET AL.